Background

Lung squamous cell carcinoma (LUSC) is associated with poor clinical prognosis and lacks available targeted therapy. Given that the major threat of cancer is metastasis, delineation of the molecular mechanism underlying it would help devise therapeutic strategies.

Objective

To investigate the functional role of protocadherin alpha 3 (PCDHA3) in LUSC, as well as investigate the underlying molecular mechanism.

Methods

Data for PCDHA3 expression and clinical information in The Cancer Genome Atlas (TCGA) were extracted and analyzed in the UALCAN platform. Expression levels of PCDHA3 in LUSC cell lines were analyzed via RT-PCR and western blot. Overexpression of PCDHA3 was conducted via plasmid transfection. CCK-8 and cell cycle assays were utilized to investigate effect of PCDHA3 on cell proliferation. Transwell assay was used to detect migration and invasion. The underlying mechanism was demonstrated via western blot analysis.

Results

Our data indicate that PCDHA3 was low expressed in three kinds of LUSC cell lines and best in H520 cells. Furthermore, overexpression of PCDHA3 could significantly impair LUSC cells proliferation, invasion and migration. Moreover, PCHDA3 repressed the biomarkers of mesenchymal (N-cadherin, fibronectin and vimentin) and increased expression of epithelial markers (E-cadherin and α-catenin). On the other hand, PCDHA3 overexpression partially blocked epithelial-mesenchymal transition.

Conclusions

PCDHA3 suppressed the LUSC cells proliferation, invasion and migration via inhibiting the expression of EMT signatures, suggesting that PCDHA3 could serve as a valuable therapeutic target for LUSC therapy.

中文翻译：

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原钙粘蛋白α3抑制肺鳞状细胞癌转移和上皮间质转化

背景

肺鳞状细胞癌（LUSC）与不良临床预后相关，缺乏可用的靶向治疗。鉴于癌症的主要威胁是转移，描述其背后的分子机制将有助于制定治疗策略。

客观的

研究 protocadherin alpha 3 (PCDHA3) 在 LUSC 中的功能作用，并研究潜在的分子机制。

方法

在 UALCAN 平台中提取和分析癌症基因组图谱 (TCGA) 中PCDHA3表达和临床信息的数据。通过 RT-PCR 和蛋白质印迹分析 LUSC 细胞系中 PCDHA3 的表达水平。PCDHA3的过表达通过质粒转染进行。CCK-8 和细胞周期测定用于研究 PCDHA3 对细胞增殖的影响。Transwell测定用于检测迁移和侵袭。通过蛋白质印迹分析证明了潜在的机制。

结果

我们的数据表明PCDHA3在三种LUSC细胞系中低表达，在H520细胞中表达最好。此外，PCDHA3的过表达可显着损害 LUSC 细胞的增殖、侵袭和迁移。此外，PCHDA3 抑制间充质的生物标志物（N-钙粘蛋白、纤连蛋白和波形蛋白）并增加上皮标志物（E-钙粘蛋白和 α-连环蛋白）的表达。另一方面，PCDHA3过表达部分阻断了上皮-间质转化。

结论

PCDHA3通过抑制EMT特征的表达来抑制LUSC细胞的增殖、侵袭和迁移，表明PCDHA3可以作为LUSC治疗的有价值的治疗靶点。